A non-human primate model has been established in rhesus monkeys to develop methods for gene insertion into hematopoietic stem cells. Any disease affecting cellular derivatives of the bone marrow or lymphoid systems might effectively be treated if gene insertion into hematopoietic stem cells could regularly be accomplished. We have shown that gene insertion into primate stem cells can be achieved with retroviral vectors although transfer is relatively inefficient. Bone marrow is harvested and cultured in vitro in the presence of hematopoietic growth factors that promote cell survival and stimulate cell division. The recipient animal receives high dose irradiation to ablate remaining marrow cells and then the autologous marrow cells, exposed in vitro to a recombinant retrovirus, are reinfused. Long-term reconstitution with retrovirally marked cells has been demonstrated with derivatives of genetically modified stem cells present in both lymphoid and myeloid compartments. An immunological method has been utilized for purifying stem cells based on expression of the CD34 antigen. CD34 positive cells have been shown to be capable of reconstitution of both the lymphoid and myeloid systems and retroviral mediated gene insertion into these purified stem cell populations has been achieved.